D1 receptor blockade stereospecifically impairs the acquisition of drug-conditioned place preference and place aversion

Acquas, E.; Chiara, G. Di

doi:10.1097/00008877-199410000-00001

Cited by 98Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchSchizophrenia research and treatment

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D1 receptor blockade stereospecifically impairs the acquisition of drug-conditioned place preference and place aversion

Acquas, E., Chiara, G. Di·1994·Behavioural Pharmacology

DOI 10.1097/00008877-199410000-00001

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Abstract

The motivational effects of dopamine (DA) D1 receptor blockade and its influence on the motivational effects of amphetamine (1.0mg/kg s.c.), morphine (1.0mg/kg s.c.) and lithium (40mg/kg s.c.) were studied in a place-conditioning paradigm. Drugs tested were two potent D1 receptor antagonists, SCH 23390 and SCH 39166, that differ in the poor affinity of the latter for 5-HT(2) receptors, and SCH 23388, the inactive enantiomer of SCH 23390. SCH 23390 and SCH 39166, at low doses (12.5 and 25µg/kg s.c.), paired for 30min with one compartment, elicited place aversion. Higher doses of the D1 antagonists or pairing for 60min with one compartment failed to elicit place aversion. SCH 39166 (50µg/kg s.c.) paired with both compartments completely prevented the place-aversion elicited by SCH 23390 (12.5µg/kg s.c.). SCH 23390 and SCH 39166 at low doses (12.5 and 25µg/kg s.c. respectively), paired with both compartments, abolished amphetamine-induced place preference. The D1 antagonists also impaired the acquisition of morphine-induced place preference and lithium-induced place aversion but only at higher doses (50 and 100µg/kg s.c.). These effects were stereospecific as the inactive enantiomer SCH 23388, up to a dose of 500µg/kg s.c. failed to impair the acquisition of amphetamine and morphine-induced place preference. It is concluded that DA plays a dual role in motivation: one role is that of assigning motivational valence to stimuli in relation to changes in DA transmission; another role of DA relates to the learning process involved in the acquisition of positive as well as negative incentive properties by otherwise neutral stimuli (incentive learning).

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Conditioning, driven by stimulation of D1 receptors in the nucleus accumbens, explains the addictive potential of drugs.
“Conditioning, driven by stimulation of D1 receptors in the nucleus accumbens, explains the addictive potential of drugs 47,48 .”
From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [48]

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Authors: Acquas, E., & Chiara, G. D.
Affiliations: University of Cagliari (IT)
Corresponding author: Chiara, G. Di
ORCID: Acquas, E.
Venue: Behavioural Pharmacology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 1994-10
Volume: 5
Issue: 6
Pages: 555-569
ISSN: 0955-8810 (ISSN-L)
DOI: 10.1097/00008877-199410000-00001
OpenAlex: W2088891858
Cited by: 98
References: 0
Citations by year: 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 5 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 4 · 2012: 5
FWCI: 1.16
Type: journal article
Language: en
Open access: closed
Locations: Behavioural Pharmacology (publishedVersion)
PubMed (publishedVersion)
UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords: dopamine D1 receptor, dopamine D1 receptor antagonist, stereospecificity, place conditioning, place preference, place aversion, amphetamine, morphine, lithium, incentive learning, SCH 23390, SCH 39166, enantiomers

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D1 receptor blockade stereospecifically impairs the acquisition of drug-conditioned place preference and place aversion

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